This program project has been involved in many areas of clinical research over the years, with activities in epidemiology, surgery, genetics and pharmacology of epilepsy. The epidemiological studies have shown that the elderly have the highest incidence and prevalence of epilepsy of any age group, even higher than in the pediatric segment. Furthermore, the elderly are the most rapidly growing segment of the population. Very little is known regarding the effect of aging, co-educations, and co-morbidity on the pharmacology of the antiepileptic drugs (AEDs). This 5 year proposal will use the information and expertise developed in previous years to study metabolism of antiepileptic medications in vitro, in vivo in a large, nursing home population of elderly, to evaluate outcomes of AED use and study race and gender effects on the development of epilepsy. Our epidemiological expertise will be used to evaluate the co- morbidity of epilepsy and vascular disease using the ARIC data base. A major strength of this proposal is the access to large groups of elderly, with over 60,000 elderly in nursing homes through PCA and Beverly Enterprises and 16,000 in the ARIC data base. The elderly especially in these nursing homes are vulnerable to improper AED use and drug toxicity until evidence based guidelines can be developed.